Cell subsets that define immune recovery merge over time

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

While clinical outcomes for autologous hematopoietic cell transplantation (AHCT) were comparable between HIV-positive and HIV-negative patients, distinctions were seen in terms of immune recovery of specific peripheral blood mononuclear cell subsets during the first year post-AHCT.

Note that differences diminished as patients recovered post-transplant and distinct clusters of cells of HIV-infected patients tended to merge with other cells over time, reflecting a more normal looking distribution.

SAN DIEGO -- While clinical outcomes for autologous hematopoietic cell transplantation (AHCT) were comparable between HIV-positive and HIV-negative patients, distinctions were seen in terms of immune recovery of specific peripheral blood mononuclear cell (PBMC) subsets during the first year post-AHCT, although differences diminished as patients recovered post-transplant, researchers reported here.

There were fewer cell subsets significantly different at day 365 compared to day 56 or 120 in all comparisons, according to Mateusz Makowski, PhD, with Emmes of Rockville, Md., and colleagues.

Distinct clusters of cells of HIV-infected patients tended to merge with other cells over time, reflecting a more normal looking distribution, he said in a presentation at the American Society of Hematology annual meeting.

"What we are seeing is that, as time goes on, the subsets of cells begin to get closer to each other," Makowski told MedPage Today. His group looked at three subsets -- HIV-positive, HIV-negative, and healthy controls -- and "found there was no difference in survival between HIV-positive and HIV-negative transplant patients," he said. "It tells us at least that in these 18 cell subsets that define immune recovery, the groups are getting closer together. There has been a huge paradigm shift that makes these HIV patients eligible for transplants."

Their analysis of cellular immunome was performed using five-color flow cytometry. Comparisons were made between HIV-positive and HIV-negative cohorts of PBMC subsets at 56, 180, and 360 days post-AHCT.

The HIV-negative cohort was collected from 30 multiple myeloma patients enrolled in a longitudinal immune recovery study after AHCT (median age 52.5 years, 57% male, no post AHCT exposure to immunomodulators or other treatment). The control patients were 72 healthy volunteers (median age of 49, 53% male ).

"A Wilcoxon rank sum test was utilized to compare the HIV-positive and HIV-negative groups to controls and to each other at each time point for 18 immune cell subsets common to all three panels. An unsupervised analysis was performed utilizing a principal component analysis (PCA) to look for overall differences in the cohorts, " the authors explained.

"These findings may be consistent with expanded populations of chronically activated cytotoxic T lymphocytes in HIV-positive transplant patients," they explained.

They also reported a pattern of both HIV-positive and HIV-negative transplant patients clustering closer to controls as patients recovered from AHCT.

"These data provide further justification supporting the use of autologous hematopoietic cell transplantation as an option for HIV-positive patients provided they meet standard transplant criteria," the authors stated.

Patients with controlled HIV, but not necessarily undetectable viral loads, and with HIV-related lymphoma were eligible for the trial, and "that really represents the majority of the patients that we see," said Stefan Barta, MD, of Fix Chase Center/Temple Health in Philadelphia.

At his institution, HIV-positive patients do as well as HIV-negative patients and historical controls, Barta told MedPage Today. The findings from the current study won't necessarily come as a surprise to clinicians who treat HIV-positive patients, but it may be news for clinicians who treat patients in the community setting and don't have a lot of experience with HIV, added Barta, who was not involved in the study.

"We have transplanted patients with HIV, and this study does confirm our experience," he said.

He added that the immune recovery analysis "does show that there are differences among the groups in how they recover, but it certainly does not indicate that recovery is worse for the the HIV patients."

He noted that AHCT may benefit HIV patients more than others. "We are altering the immune system milieu, and may be allowing the emergence of healthier T-cells, which could benefit HIV patients," he explained.

Study co-author Lawrence Kaplan, MD, of the University of California San Francisco, told MedPage Today that "the bottom line is that by the time you get out to a year after transplant, everybody's immune systems look pretty much the same -- the HIV-positive patients, the HIV-negative patients, and the healthy controls who didn't have transplants. At this particular moment in medicine, there are no substantial differences in outcomes, or in treatment, or in related toxicities in HIV patients undergoing transplantation relative to uninfected patients undergoing transplantation."

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